Statin Therapy-Evidence Beyond Lipid Lowering Contributing to Plaque Stability

Abstract

Primarily statin drugs inhibit hepatic 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is responsible for the reduction in circulating low-density lipoprotein (LDL) cholesterol. Several findings from recent research studies indicate that statins have multiple actions that favorably influence key factors involved in the atherogenic process. These so-called pleiotropic properties affect various aspects of cell function, inflammation, coagulation, and vasomotor activity. These effects are mediated either indirectly through LDL cholesterol reduction or via a direct effect on cellular functions. Such actions may contribute to the early cardiovascular benefit observed in several outcome trials with statin drugs therapy. Although many of the pleiotropic properties of statins may be a class effect, some may be unique to certain agents and account for differences in their pharmacological activity. This review summarise the results of the major outcome trials of statins and non-statins therapy and the possible mechanisms beyond lipid lowering contributing to plaque stability.

Statins Reduce Peri-procedural Complications in Carotid Stenting

“…In this study, statins showed LDL-cholesterol lowering effects; however, considering the impact of other multiple pleiotropic effects caused by statins, such as effects on endothelial function, inflammation, arterial myocyte proliferation, migration and apoptosis, plaque stability, platelet activity, and the coagulation process, the lowering of LDL-cholesterol is not the only relevant parameter for the achievement of successful risk reduction. 11,35 As in other studies, LDL-cholesterol levels did not show a significant effect on any endpoint. Results of various studies suggest that treatment with statins should be indicated in accordance with the global vascular risk profile and not primarily on base-level LDLcholesterol concentrations.…”

The Effect of Statin Use on Embolic Potential During Carotid Angioplasty and Stenting

“…5,6,8,9 Collectively, these actions are known as the pleiotropic effects of statins. These unexpected beneficial actions seen with HMG-CoA reductase inhibitors result from improved endothelial function, less oxidized LDL uptake by endothelial cells and macrophages, increased nitric oxide synthase expression, decreased migration of monocytes and differentiation into activated macrophages, and less overall inflammation.…”

Macrophages: An elusive yet emerging therapeutic target of atherosclerosis

“…Here probably, a combination of PPAR ligands and naturally occurring ligands like 24(S), 25-epoxycholesterol may work better, but again this need to be tested. Treatment of macrophages with the PPARg ligands troglitazone and pioglitazone upregulated the expression of the SREBP-2 target genes HMG-CoA synthase and HMG-CoA reductase [202][203][204][205] ; however, in HepG2 and Caco-2 cells PPARg activation by troglitazone lowers the cholesterol synthesis by reducing the concentration of nuclear SREBP-2 and successive downregulation of its target genes involved in cholesterol synthesis. 206 These results indicate that PPARg and SREBP-2 interaction and regulation may be tissue/cell-specific which makes the targeting of this pathway more challenging.…”